The present invention relates to processes for isolating fluorinated products in fluorination reactions that utilize 4-tert-butyl-2,6-dimethylphenylsulfur trifluorides (Fluolead). Fluolead has recently been developed as a very useful deoxofluorinating agent with high thermal stability, ease of handling, unusual resistance to aqueous hydrolysis, and wide application [see, for example, J. Am. Chem. Soc., 2010, 132, 18199-18205 and its supporting information]. Fluolead's excellent and unique properties are based on extremely high lipophilicity caused by a tert-butyl and two methyl substituents on a benzene ring. Fluolead fluorinates many kinds of organic compounds such as alcohols, aldehydes, ketones, carboxylic acids, thioketones, thioesters, dithioesters, thiocarbonate, and dithiocarbonates to give the corresponding fluorinated compounds in high yields. These fluorinated compounds are useful for the preparation or development of medicines, agrochemicals, liquid crystals, and the like (see, for example, J. Fluorine Chem. 2006, Vol. 127, pp. 992-1012; Chem. & Eng. News, June 5, pp. 15-32 (2006); “Modern Fluoroorganic Chemistry—Synthesis, Reactivity, Applications”, Wily-VCH, Weinheim (2004), pp. 203-277; Angew. Chem. Ind. Ed., Vol. 39, pp. 4216-4235 (2000)). Therefore, Fluolead has high potential to apply to these industries due to its high fluorination capability.
However, there is a drawback in fluorination reactions using Fluolead. Fluolead reacts with an organic compound to form an equimolar amount of a byproduct, 4-tert-butyl-2,6-dimethylphenylsulfinyl fluoride (represented by compound (I)), along with the fluorinated product. The byproduct is difficult to separate from the fluorinated product and results in a loss of product purity and therefore product effectiveness (see equation 1 for reaction overview).

The byproduct (I) cannot be removed from the organic layer of the reaction mixture by washing it with an aqueous alkaline solution (a required step in the isolation of the fluorinated products), because the byproduct (I) undergoes a disproportionation reaction during hydrolysis to substantially form thiolsulfonate (compound (III)) and sulfonate salt (compound (IV)), as shown in the following scheme 1:

Although compound (IV) is soluble in an aqueous layer, compound (III) is not. Therefore, the fluorinated products cannot be separated from byproduct (III). The extraordinary easy occurrence of the disproportionation of byproduct (I) to (III) via (II) is owing to its high lipophilicity caused by its unique chemical structure, that is, one tert-butyl and two methyl substituents on a benzene ring. Therefore, the fluorinated compounds are contaminated with a significant amount of solid thiolsulfonate (III). Column-chromatography for the separation of compound (III) from the fluorinated products requires is relatively costly, and is not suitable for the large scale production. Alternatively, fractional distillation for the separation has limited scope, because it cannot be applied to solid fluorinated products. Therefore, the solution to producing industrial amounts of fluorinated products using Fluolead requires a new approach.
The present invention is directed toward overcoming the problem discussed above.